Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1

Jessica L L Robinson, Stewart Macarthur, Caryn S Ross-Innes, Wayne D Tilley, David E Neal, Ian G Mills, Jason S Carroll

Research output: Contribution to journalArticlepeer-review

198 Citations (Scopus)

Abstract

Breast cancer is a heterogeneous disease and several distinct subtypes exist based on differential gene expression patterns. Molecular apocrine tumours were recently identified as an additional subgroup, characterised as oestrogen receptor negative and androgen receptor positive (ER- AR+), but with an expression profile resembling ER+ luminal breast cancer. One possible explanation for the apparent incongruity is that ER gene expression programmes could be recapitulated by AR. Using a cell line model of ER- AR+ molecular apocrine tumours (termed MDA-MB-453 cells), we map global AR binding events and find a binding profile that is similar to ER binding in breast cancer cells. We find that AR binding is a near-perfect subset of FoxA1 binding regions, a level of concordance never previously seen with a nuclear receptor. AR functionality is dependent on FoxA1, since silencing of FoxA1 inhibits AR binding, expression of the majority of the molecular apocrine gene signature and growth cell growth. These findings show that AR binds and regulates ER cis-regulatory elements in molecular apocrine tumours, resulting in a transcriptional programme reminiscent of ER-mediated transcription in luminal breast cancers.

Original languageEnglish
Pages (from-to)3019-27
Number of pages9
JournalThe EMBO Journal
Volume30
Issue number15
DOIs
Publication statusPublished - 03 Aug 2011

Keywords

  • Apocrine Glands
  • Breast Neoplasms
  • Cell Line, Tumor
  • DNA
  • Hepatocyte Nuclear Factor 3-alpha
  • Humans
  • Promoter Regions, Genetic
  • Protein Binding
  • Receptors, Androgen
  • Transcription, Genetic

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